Exciting developments in several fields are converging to offer an ever more comprehensive explanation of cancer and aging. Telomerase has emerged as a major determinant of cellular immortality. Oncogenic proteins target cell cycle controls and checkpoints for modification or inactivation. Networks of developmental and growth regulatory signals gain independence from physiological controls. New insights into DNA repair extend the role of genetic and genomic instability as initiating factor in oncogenesis; and novel mechanisms of chromatin remodeling broaden our understanding of transcriptional controls. Progress in transgenic and knock-out technologies yields animal model systems that closely mimic human cancers. The origins of genetic and genomic instability remain one of the central problems in oncogenesis. It has links to telomerase, to cell cycle controls, to signaling and to chromatin. Understanding the causes of this instability is an important goal of animal model systems. Completion of the human genome sequence and extensive expression profiling are not only generating tremendous wealth of new knowledge but are also driving the synthesis of diverse data into coherent systems of understanding.